Parinaud syndrome

David Goldemund M.D.
Updated on 10/08/2024, published on 31/05/2024

Parinaud syndrome is caused by disturbance of the midbrain tectum and is characterized by upward gaze palsy, convergence retraction nystagmus, light-near dissociation, and bilateral lid retraction
syndrome is named after French ophthalmologist Henri Parinaud
synonyms: dorsal midbrain syndrome, Sylvian aqueduct syndrome, pretectal syndrome

Anatomy and pathophysiology

The vertical gaze center lies in the rostrodorsal portion of the midbrain and involves several key structures:

rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
- plays a critical role in the generation of vertical saccades; it is involved in initiating and coordinating rapid eye movements in the vertical plane
the interstitial nucleus of Cajal (INC)
- essential for vertical gaze stabilization
the nucleus of Darkschewitsch
the nucleus of the posterior commissure (involved primarily in downward gaze)
oculomotor nucleus complex (CN III)
- sends motor signals to the superior rectus, inferior rectus, and other muscles essential for vertical gaze

Parinaud syndrome leads to upward gaze paresis due to riMLF and INC lesion; downgaze is relatively preserved; it is typically only affected by large space-occupying lesions or bilateral lesions
light-near dissociation (pseudo-Argyll Robertson pupils)
- pupils accommodate but do not react to light
- caused by damage to the pretectal and Edinger-Westphal nuclei or the decussating fibers of the pretectal nucleus in the posterior commissure
convergence-retraction nystagmus – due to abnormal burst activity in the pretectal area, causing intermittent co-contraction of the medial recti (convergence) + simultaneous superior and inferior rectus (retraction) during attempted upward gaze
bilateral lid retraction (Collier sign) due to loss of the supranuclear inhibitory input to the third nerve nucleus; the levator palpebrae superioris receives constant stimulation via the oculomotor nerve, resulting in lid retraction

riMLF is a crucial structure involved in the control of vertical eye movements
located in the rostral part of the midbrain, near the midbrain-diencephalon junction, adjacent to the medial longitudinal fasciculus (MLF)
primarily responsible for initiating and coordinating rapid vertical eye movements (saccades)
- receives inputs from various cortical and subcortical regions involved in eye movement control, including the frontal eye fields and superior colliculus
- sends direct excitatory inputs to the oculomotor (CN III) and trochlear (CN IV) nuclei, which innervate the extraocular muscles responsible for vertical eye movements
riMLF works in conjunction with other nuclei, such as the interstitial nucleus of Cajal (INC), to integrate and execute vertical eye movements
lesions in the riMLF can lead to vertical gaze palsy, particularly affecting the ability to generate vertical saccades

INC plays a critical role in the control of eye movements, particularly in maintaining vertical gaze and contributing to the stabilization of eye position
it integrates signals from the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) for vertical saccades and smooth pursuits and is involved in the vestibulo-ocular reflex (VOR)
- receives input from various brainstem structures involved in eye movement control, such as the superior colliculus and the riMLF
- sends projections to the oculomotor and trochlear nuclei, which innervate the extraocular muscles responsible for vertical eye movements (superior and inferior rectus, superior and inferior oblique muscles)

the nucleus is located in the periaqueductal gray matter ventral to the aqueduct at the level of the superior colliculi
it has two major components:
- a medially situated parasympathetic nucleus, called the Edinger-Westphal nucleus (or accessory autonomic nucleus), which innervates the intraocular muscles (the sphincter pupillae muscle and the ciliary muscle)
- a larger and more laterally situated nuclear complex for four of the six extraocular muscles (the superior, inferior, and medial rectus muscles and the inferior oblique muscle). There is also a small nuclear area for the levator palpebrae muscle

ischemic stroke – occlusion of pretectal perforators or dorsal penetrating branches from the posterior cerebral artery (PCA), incl. the quadrigeminal artery
- vascular causes are more common in the elderly
external compression (hydrocephalus, pineal tumors, aneurysm)
brainstem tumors (glioma), hemorrhage, or infections (e.g., toxoplasmosis)
multiple sclerosis (Moreira et al., 2012
Progressive Supranuclear Palsy (PSP)
- a rare neurodegenerative disorder characterized by vertical gaze palsy, postural instability, and cognitive impairment
Whipple’s disease (GIT disorders, dementia, uveitis)

upward gaze palsy (“sunset” eyes)
light-near dissociation
- normal or slightly dilated pupils
- no light reaction with preserved reaction to accommodation (pseudo-Argyll-Robertson pupil)
convergence-retraction nystagmus during convergence
eyelid retraction (Collier sign)

bilateral paralysis of the muscles elevating the eyeball (RS and Ol – “double elevator palsy”)
pseudo-dorsal midbrain syndrome in myasthenia gravis
- search for fatigable weakness, variable symptoms, and response to edrophonium or ice pack test
local causes of restricted upward movement due to orbital lesions
- thyroid eye disease – immune-mediated enlargement of extraocular muscles
- Brown’s syndrome of the superior oblique tendon – dysfunction of the superior oblique tendon sheath, causing mechanical restriction of elevation, particularly in adduction
congenital or age-related limitation of upward movement